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Objectives: The quality of life after extracorporeal membrane oxygenation therapy has emerged as an important issue for extracorporeal membrane oxygenation survival; however, its association with long-term prognosis has not been identified. We investigated the changes in the quality of life after extracorporeal membrane oxygenation among the survivors and examine the association between a worse quality of life and 3-year all-cause mortality.Design: This was a population-based cohort study.Setting: Data were obtained from the National Health Insurance Service database in South Korea.Patients: Adult individuals (≥ 18 yr old) who received extracorporeal membrane oxygenation therapy from 2006 to 2017 were included. Extracorporeal membrane oxygenation survivors were defined as patients who had survived for 1-year after the initiation of extracorporeal membrane oxygenation therapy.Interventions: None.Measurements and Main Results: The income level, employment status, and registered disability were examined before and 1-year after extracorporeal membrane oxygenation therapy. The decreased income level, job loss, and newly acquired disability were considered as change in the quality of life among extracorporeal membrane oxygenation survivors. A total of 5,821 adult extracorporeal membrane oxygenation survivors were included in the final analysis, and 2,959 patients (50.8%) experienced quality of life change. Specifically, 1,782 patients (30.6%) experienced a decrease in income, 682 (11.7%) lost their jobs, and 1,540 (26.5%) had a new disability within 1-year after extracorporeal membrane oxygenation therapy. In the multivariable Cox regression model, newly acquired disability was associated with 2.31-fold higher 3-year all-cause mortality among extracorporeal membrane oxygenation survivors (hazard ratio, 2.31; 95% CI, 1.79-2.97; p < 0.001), while job loss (p = 0.180) and decreased income (p = 0.993) were not associated with the 3-year all-cause mortality.Conclusions: At 12 months after extracorporeal membrane oxygenation therapy, nearly half survivors experienced quality of life worsening such as unemployment, decreased income, and new disability. Additionally, among the three factors, acquiring a new disability might significantly increase the 3-year mortality. This is the first study to report the association between changes in the quality of life and long-term prognosis in extracorporeal membrane oxygenation survivors. [ABSTRACT FROM AUTHOR]